PROJECT SUMMARY/ABSTRACT Graphene-family nanomaterials (GFNs) are emerging as commercially important carbon nanomaterials with potential applications in nanoelectronics and energy storage, nanomedicine, nanocomposites, and environmental sensing and remediation. Goal: Project 2 will evaluate potential adverse human health impacts of novel graphene-based composite barriers developed in Project 4 for containment of vapor toxicants at Superfund and toxic waste sites. Hypothesis: It is hypothesized that lateral dimension, surface oxidation state, and biopersistence are primary determinants of graphene-family nanomaterial toxicity. Four Specific Aims will be carried out by an interdisciplinary research team that includes a materials scientist and a toxicologist to test this hypothesis. Specific Aim 1: Determine the role of lateral dimension of GFNs on macrophage uptake, motility, and toxicity. Specific Aim 2: Systematically assess the effects of surface oxidation state and aging on ROS generation, toxicity, and biodurability of GFNs. Specific Aim 3: Evaluate the toxicity of complex graphene-copper hybrid materials. Specific Aim 4: Rank pristine, surface-modified, and complex metal-hybrid GFNs based on acellular and in vitro toxicity assays and validate this ranking by assessing toxicity and biopersistence of selected materials in 3-dimensional lung microtissues and in mice. Methods and Expected Outcome: Novel graphene-based vapor barriers and copper-graphene hybrid nanocomposites will be synthesized and characterized in Project 4 using novel, state-of-the-art techniques. A combined in vitro ? in vivo approach will be used in Project 2 to assess the impact of aging and systematic chemical modification on macrophage uptake, motility, and toxicity as well as on lung clearance, biopersistence, and fibrosis. This integrated, interdisciplinary research approach will enable safe design and fabrication of GFNs for commercial applications and environmental remediation with minimal adverse human health impacts.